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Enhancement of Naturally Occurring Human Spontaneous Monocyte-mediated Cytotoxicity by cis-Diamminedichloroplatinum(II)

Metabolism Branch [E. S. K., A. V. M.] and the Laboratory of Molecular Pharmacology [L. A. Z.], National Cancer Institute, NIH, Bethesda, Maryland 20205

The effect of the antineoplastic agent cis-diamminedichloroplatinum(II) (cis-DDP) on spontaneous cytotoxicity of human mononuclear cells in vitro was assessed. cis-DDP enhanced spontaneous monocyte-mediated cytotoxicity 300% compared to control values. Further, this spontaneous monocyte killing developed earlier (3 to 4 days) than did that of untreated cells (5 to 7 days). Since monocyte cytotoxicity is under the control of lymphocyte suppressor cells, the effect of cis-DDP on separated populations of lymphocytes and monocytes was examined. Unlike X-irradiation which enhanced monocyte cytotoxicity through the indirect pathway of inactivation of lymphocyte suppressors, cis-DDP directly stimulated the monocyte population. Direct stimulation of killer monocytes may be an important mechanism of the antitumor effect of cis-DDP.

¹ To whom requests should be addressed, at Metabolism Branch, National Cancer Institute, Building 10, Room 4N117, Bethesda, Md. 20205.

Received 1/24/80. Accepted 5/21/80.